Sample holders and methods of using them

ABSTRACT

Certain embodiments described herein are directed to sample holders that can be used to retain a sample support effective for use in direct sample analysis. In some embodiments, the sample support can include a first and a second plate with apertures to permit a sample to be analyzed using direct sample analysis.

TECHNOLOGICAL FIELD

Certain features, aspects and embodiments are directed to sample holdersand methods of using them. In certain examples, the sample holders canbe configured for use in direct sample analysis.

BACKGROUND

Direct sample analysis permits analysis of a sample by directlyintroducing the sample into an instrument. If desired, front-endchromatography separation can be omitted prior to analysis of thesample.

SUMMARY

Certain features, aspects and embodiments described herein are directedto sample holders that can be used to hold or retain a sample support topermit direct sample analysis of a sample on the sample support. Theexact configuration of the sample holder may vary, and illustrations ofdifferent types of sample holders are described in detail below.

In one aspect, a sample holder comprising a first plate comprising atleast one aperture to permit a sample on a sample support to becontacted by fluid for direct sample analysis, the first platecomprising a retaining device is provided. In some embodiments, thesample holder can also comprise a second plate rotatably coupled to thefirst plate and comprising a corresponding aperture to the at least oneaperture of the first plate, the second plate configured to rotate toengage the first plate and retain the sample support between the firstplate and the second plate, in which the retaining device of the firstplate is configured to engage the second plate to the first plate in afirst position to retain the sample support between the first plate andthe second plate and to disengage the second plate from the first platein a second position to permit removal of the sample support from thesample holder.

In certain examples, each of the first plate and the second platecomprise a plurality of apertures to permit sample loading on the samplesupport. In other examples, the first plate and second plate areconfigured to permit contact of the sample by fluid at one side of thesample holder to ionize sample on the sample support. In someembodiments, the first plate and second plate are configured to permitflow of the ionized sample from a second side of the sample holder. Insome examples, the retaining device of the first plate is configured toslide laterally to engage the second plate in the first position anddisengage the second plate in the second position. In other embodiments,the retaining device comprises two sliding devices each configured toslide laterally to disengage the first plate from the second plate andto slide medially to engage the first plate to the second plate. Infurther embodiments, the first plate and the second plate areasymmetric. In other embodiments, the first plate and the second plateeach comprise an effective material to permit contact of sample on thesample support by a plasma without substantial degradation of the firstplate and the second plate. In additional embodiments, each of the firstplate and the second plate comprises stainless steel. In someembodiments, at least one of the first plate and the second platecomprises a plastic. In certain examples, the plastic ispolyetheretherketone. In further examples, each of the first plate andthe second plate comprise the same number of apertures. In additionalembodiments, the apertures of the first plate and the second platecomprise the same geometry. In some examples, the geometry is circular.In certain embodiments, the circular apertures have a center-to-centerspacing of about 0.2 inches to about 0.75 inches, e.g., about 0.5inches. In certain examples, at least one of the first plate and thesecond plate comprises an alignment mechanism for receiving the samplesupport. In further embodiments, one of the first plate and the secondplate comprises a ball and the other plate comprises a socket. In someembodiments, the first plate and second plate are coupled to each otherthrough a hinge. In further examples, the first plate comprises adifferent number of apertures than the second plate. In additionalexamples, the sample holder is configured to retain the sample supportbetween the first plate and the second plate in the first position ofthe retaining device without the use of an external fastener.

In another aspect, a sample holder configured to retain a sample supportfor direct sample analysis of a sample on the sample support, the sampleholder comprising a first plate coupled to a second plate through atleast one joint, the first plate comprising a sliding device configuredto hold the second plate towards the first plate in a first position andto permit rotation of the second plate away from the first plate in thesecond position, in which the holding of the second plate towards thefirst plate is effective to retain the sample support between the firstplate and the second plate is provided.

In certain embodiments, each of the first plate and the second platecomprise a plurality of apertures to permit sample loading on the samplesupport. In other embodiments, the first plate and second plate areconfigured to permit contact of the sample by fluid at one side of thesample holder to ionize sample on the sample support. In additionalembodiments, the first and second plates are configured to permit flowof the ionized sample from a second side of the sample holder. Infurther embodiments, the sliding device comprises two sliding deviceseach configured to slide laterally to disengage the first plate from thesecond plate and to slide medially to engage the first plate to thesecond plate. In some examples, the sliding device comprises a singlesliding device configured to slide laterally to disengage the firstplate from the second plate and to slide medially to engage the firstplate to the second plate. In some embodiments, the first plate and thesecond plate are asymmetric. In further embodiments, the first plate andthe second plate each comprise an effective material to permit contactof sample on the sample support by a plasma without substantialdegradation of the first plate and the second plate. In otherembodiments, each of the first plate and the second plate comprisesstainless steel. In additional examples, at least one of the first plateand the second plate comprises a plastic. In some embodiments, theplastic is polyetheretherketone. In other embodiments, each of the firstplate and the second plate comprise the same number of apertures. Inadditional embodiments, the apertures of the first plate and the secondplate comprise the same geometry. In certain examples, the geometry iscircular. In some embodiments, the circular apertures have acenter-to-center spacing of about 0.25 to about 0.75 inches, e.g., about0.5 inches. In some embodiments, at least one of the first plate and thesecond plate comprises an alignment mechanism for receiving the samplesupport. In further embodiments, the joint is configured as aball-and-socket joint. In certain examples, the joint is configured as ahinge joint. In some examples, the first plate comprises a differentnumber of apertures than the second plate. In further examples, thesample holder is configured to bias the second plate toward the firstplate without the use of an external fastener.

In an additional aspect, a sample holder for direct sample analysis, thesample holder comprising a first plate comprising at least one apertureto permit a sample on a sample support to be contacted by fluid fordirect sample analysis, the first plate comprising a retaining device isdescribed. In certain embodiments, the holder can comprise a secondplate comprising an integral sample support and configured to removablycouple to the first plate, the second plate further configured to rotateto engage the first plate, in which the retaining device of the firstplate is configured to engage the second plate to the first plate in afirst position and to disengage the second plate from the first plate ina second position.

In certain examples, each of the first plate and the second platecomprise a plurality of apertures to permit sample analysis of sampleson the sample support. In other examples, the first plate and secondplate are configured to permit contact of the sample by fluid at oneside of the sample holder to ionize sample on the sample support. Insome embodiments, the first plate and second plate are configured topermit flow of the ionized sample from a second side of the sampleholder. In other embodiments, the retaining device of the first plate isconfigured to slide laterally to engage the first plate in the firstposition and disengage the first plate in the second position. Infurther embodiments, the retaining device comprises two sliding deviceseach configured to slide laterally to disengage the first plate from thesecond plate and to slide medially to engage the first plate to thesecond plate. In certain examples, the first plate and the second plateare asymmetric. In some embodiments, the first plate and the secondplate each comprise an effective material to permit contact of sample onthe sample support by a plasma without substantial degradation of thefirst plate and the second plate. In certain examples, each of the firstplate and the second plate comprises stainless steel. In additionalexamples, at least one of the first plate and the second plate comprisesa plastic. In some embodiments, the plastic is polyetheretherketone. Inother examples, each of the first plate and the second plate comprisethe same number of apertures. In certain embodiments, the apertures ofthe first plate and the second plate comprise the same geometry. In someexamples, the geometry is circular. In additional examples, the circularapertures have a center-to-center spacing of about 0.25 inches to about0.75 inches, e.g., about 0.5 inches. In other embodiments, at least oneof the first plate and the second plate comprises an alignment mechanismfor receiving the sample support. In some examples, one of the firstplate and the second plate comprises a ball and the other platecomprises a socket. In certain embodiments, the first plate and thesecond plate are coupled to each other through a hinge. In someexamples, the first plate comprises a different number of apertures thanthe second plate. In some embodiments, the sample holder is configuredto retain the sample support between the first plate and the secondplate in the first position of the retaining device without the use ofan external fastener.

In another aspect, a kit comprising a first plate comprising at leastone aperture to permit a sample on a sample support to be contacted byfluid for direct sample analysis, the first plate comprising a retainingdevice, and a second plate configured to removably couple to the firstplate, the second plate configured, when coupled to the first plate, torotate to engage the second plate to the first plate and retain thesample support between the first plate and the second plate, in whichthe retaining device of the first plate is configured to engage thesecond plate in a first position to retain the sample support betweenthe first plate and the second plate and is configured to disengage thesecond plate in a second position to permit removal of the samplesupport from the sample holder is provided.

In certain embodiments, the kit can include at least one sample support.In some examples, the sample support comprises a mesh. In otherexamples, the sample support is positioned in a housing. In someembodiments, the housing of the sample support is configured forinsertion between the first plate and the second plate. In otherexamples, the kit can comprise an additional second plate comprising adifferent number of apertures than the second plate. In some examples,the kit can comprise an additional first plate comprising a differentnumber of apertures than the first plate. In certain examples, the kitcan comprise an additional second plate comprising an aperture sizeddifferently than an aperture of the second plate. In other examples, thekit can comprise an additional first plate comprising an aperture sizeddifferently than the at least one aperture of the first plate. Infurther examples, the kit can comprise a plurality of sample supports,in which at least two of the sample supports are different from eachother.

In an additional aspect, a method of loading a sample for direct sampleanalysis is disclosed. In certain examples, the method comprisesproviding a sample holder comprising a first plate comprising at leastone aperture to permit a sample on a sample support to be contacted byfluid for direct sample analysis, the first plate comprising a retainingdevice, and a second plate rotatably coupled to the first plate andcomprising a corresponding aperture to the at least one aperture of thefirst plate, the second plate configured to rotate to engage the firstplate and retain the sample support between the first plate and thesecond plate, in which the retaining device of the first plate engagesthe second plate in a first position to retain the sample supportbetween the first plate and the second plate and disengages the secondplate in a second position to permit removal of the sample support fromthe sample holder.

In certain embodiments, the method comprises providing instructions forloading the sample on the sample support. In other embodiments, themethod comprises providing instructions for inserting the sample supportinto the sample holder. In some embodiments, the method comprisesproviding a sample support. In certain embodiments, the method comprisesproviding instructions for analyzing the sample on the sample supportusing direct sample analysis.

In another aspect, a method of loading a sample for direct sampleanalysis comprising providing a sample holder configured to retain asample support for direct sample analysis of a sample on the samplesupport, the sample holder comprising a first plate attached to a secondplate through at least one joint, the first plate comprising a slidingdevice configured to hold the second plate towards the first plate in afirst position and to permit rotation of the second plate away from thefirst plate in the second position, in which the holding of the secondplate towards the first plate retains the sample support between thefirst plate and the second plate is disclosed.

In certain embodiments, the method comprises providing instructions forloading the sample on the sample support. In some embodiments, themethod comprises providing instructions for inserting the sample supportinto the sample holder. In certain examples, the method comprisesproviding a sample support. In certain embodiments, the method comprisesproviding instructions for analyzing the sample on the sample supportusing direct sample analysis.

In an additional aspect, a method of loading a sample for direct sampleanalysis comprising providing a sample holder comprising a first platecomprising at least one aperture to permit a sample on a sample supportto be contacted by fluid for direct sample analysis, the first platecomprising a retaining device, and a second plate comprising an integralsample support and configured to removably couple to the first plate,the second plate further configured to rotate to engage the first plate,in which the retaining device of the first plate is configured to engagethe second plate to the first plate in a first position and to disengagethe second plate from the first plate in a second position is described.

In certain examples, the method comprises providing instructions forloading the sample on the sample support. In other examples, the methodcomprises providing instructions for inserting the sample support intothe sample holder. In some examples, the method comprises providing asample support. In certain examples, the method comprises providinginstructions for analyzing the sample on the sample support using directsample analysis.

Other aspects and attributes will become apparent to those skilled inthe art after review of the detailed description and accompanyingdrawings.

BRIEF DESCRIPTION OF FIGURES

Certain configurations are provided below for illustrative purposes onlywith reference to the accompanying figures in which:

FIG. 1 is an illustration of a sample holder in an open position, inaccordance with certain examples;

FIG. 2 is an illustration of the sample holder of FIG. 1 in a closedposition, in accordance with certain examples;

FIG. 3 is an illustration of a plate for use in another sample holder,in accordance with certain examples;

FIG. 4 is an illustration of a sample holder including the plate of FIG.3, in accordance with certain examples;

FIG. 5 is an illustration of a plate comprising a single aperture, inaccordance with certain examples;

FIG. 6 is an illustration of a sample holder including the plate of FIG.5, in accordance with certain examples;

FIGS. 7A-7C are illustrations showing plates that are asymmetric, inaccordance with certain examples;

FIG. 8 is an illustration of a sample holder comprising two rows ofaligned apertures, in accordance with certain examples;

FIG. 9 is an illustration of a sample holder comprising two rows ofoffset apertures, in accordance with certain examples;

FIGS. 10 and 10B are illustrations showing a side view of a sampleholder, in accordance with certain examples; and

FIG. 11 is an example of a system that include a direct sample analysisdevice, in accordance with certain examples.

Additional features, aspects and embodiments are described in moredetail below. It will be recognized by the person of ordinary skill inthe art, given the benefit of this disclosure, that the lengths anddimensions shown in the figures are not limiting and that many differentlengths and dimensions can be used depending on the size of the samplesupport, the system which the sample holder is to be used in and otherfactors.

DETAILED DESCRIPTION

Certain embodiments of sample holders are described below. The exactconfiguration of the sample holders including, for example, the lengthand width of the plates, size and configuration of the apertures oropenings, materials used in the plates and the like can vary dependingon the particular instrument the sample holder is to be used in and/ordepending on the nature of the sample to be analyzed. Where directsample analysis is referred to below, no particular configuration of adirect sample analysis device or system is intended to be required asbeing necessary for properly using the sample holder. For illustrationpurposes, some configurations of a direct sample analysis device orsystem are described herein. The term “plate” is used for conveniencepurposes to refer to certain components of the sample holders describedherein. The plates of the sample holders can be any device comprising asurface that is configured to engage to another surface and retain asample support between the surfaces. If desired, the surfaces maycontact the sample support in one or more areas to prevent movement ofthe sample support during analysis. In some examples, the plates contactsubstantially the same surface area of the sample support, whereas inother configurations, different plates physically contact a differentamount of surface area of the sample support. In some configurationsdescribed herein, the plates of the sample holders are generally planarstructures that can position a sample support between substantiallyparallel surfaces of the planar structures.

In certain embodiments, a sample holder configured to retain a samplesupport for direct sample analysis of a sample on the sample support isshown in FIG. 1. The sample holder 100 comprises a first plate 110 witha retaining device 115. In some examples, the retaining device 115 isgenerally configured to slide parallel to the longitudinal direction ofthe plate 110 to engage and disengage a second plate 120. If desired, asecond retaining device 125 can be present and configured similar to thesliding device 115 to assist in engagement of the plate 120. In use ofthe holder 100, the second plate 120 is rotated upward such that theplanar surface of the second plate 120 is substantially parallel to theplanar surface of the first plate 110. For example, the second plate 120can be rotatably coupled to the first plate 110 through at least onehinge or joint, such as, for example, joints 122 and 124 to permitrotation of the second plate 120 toward the first plate 110. The sampleholder 100 can be designed to position a sample support effective toretain a sample, for at least some period, to permit analysis of thesample, e.g., using direct sample analysis.

In certain examples, the retaining devices 115, 125 can be configured toslide medially to engage the second plate 120 to the first plate 110 orslide laterally to disengage the second plate 120 from the first plate110. In a typical configuration, a user would slide the retainingdevices 115, 125 laterally to disengage the second plate 120 from thefirst plate 110. A sample support such as, for example, a mesh, a screenor combinations thereof would be placed between the plates 110 and 120.Sample may be loaded onto the sample support prior to placement of thesample support between the plates 110, 120, or sample may be loaded ontothe sample support after placement of the sample support in the holder100 and engagement of the second plate 120 to the first plate 110.

In certain embodiments, FIG. 2 is an illustration of the second plate120 being engaged to the first plate 110. The retaining devices 115 and125 have been moved medially in the direction of the bold arrows shownin FIG. 2. Movement of the retaining devices 115, 125 operates to engagean upper planar surface of the second plate 120 to retain the secondplate 120 in the general position shown in FIG. 2. In particular, thesecond plate 120 can be configured with a suitable geometry such that aportion of the second plate 120 is positioned within the retainingdevices 115, 125 to capture the second plate 120 when the retainingdevices 115, 125 are in the medial position. Retention of the secondplate 120 by the retaining devices 115, 125 acts to retain or sandwichthe sample support (not shown) between the first plate 110 and thesecond plate 120. To disengage the second plate 120 from the first plate110, the retaining devices 115, 125 are moved laterally toward the endsof the first plate 110. Lateral movement of the retaining devices 115,125 acts to disengage the upper portion of the second plate 120 from theretaining devices 115, 125 and permit rotation of the second plate 120downward and away from the first plate 110. This rotation permits a userto remove the sample support and load a new sample support for furtheranalysis of sample.

In certain embodiments, the first and second plates generally includeone or more apertures that permit sample on the sample support to becontacted with a fluid, e.g., an ion beam or other fluid that canionize, atomize, vaporize or otherwise facilitate sampling of the sampleon the sample support. In certain examples, the fluid can contact thesample at one side of the sample support, and sample on the samplesupport can be carried away from the sample holder at an opposite sideof the sample holder to a device for analysis, e.g., a mass spectrometeror other suitable devices discussed herein. For example, sample can beionized using an ion beam that is incident on one side of the samplesupport, and ionized sample may be ejected and provided to a devicefluidically coupled to the sample support. The exact number of aperturespresent in the sample holder can vary, and each of the first plate andthe second plate need not include the same number of apertures. Whilethe illustrations shown in FIGS. 1 and 2 include thirteen apertures ineach of the first plate 110 and the second plate 120, this number is notrequired or limiting. In certain embodiments, the number of apertures ineach of the plates of the sample holders described herein may vary fromone to about twenty, more particularly from two to about fifteen, forexample, about five to about fifteen or about five to about thirteen.Where apertures are present in different rows as described herein, morethan twenty apertures may be present. Similarly, the particulargeometric shape selected for the apertures need not be circular or eventhe same on the first plate 110 and the second plate 120. Any geometricshape is possible, including but not limited to, circular shapes,rectangular shapes, triangular shapes, trapezoidal shapes, pentagonalshapes, hexagonal shapes, octagonal shapes and other geometric shapes.

In certain examples and referring to FIG. 3, a first plate 310 is shownthat comprises four generally rectangular apertures 312, 314, 316 and318. The first plate 310 also comprises retaining devices 330 and 335which can function similar to the retaining devices 115, 125. Ifdesired, the second plate (not shown in FIG. 3) can include the samenumber of apertures as the plate 310 or a different number of aperturesas the plate 310. In addition, the apertures of the second plate mayhave a similar geometry as the apertures of the plate 310 or a differentgeometry as the geometry of the apertures of the plate 310. In someinstances, some of the apertures of the second plate may be sized andarranged similarly to apertures of the first plate 310 and otherapertures on the second plate may be sized and arranged differently thanapertures of the plate 310. For ease of description, a second plate 320comprising the same number of apertures as the first plate 310 is shownas being present in FIG. 4. The second plate 320 comprises apertures322, 324, 326 and 328 which correspond to the openings 312, 214, 316 and318, respectively, to provide a continuous opening from one side of thesample holder 300 to the other when the second plate 320 is engaged tothe first plate 310 using the retaining devices 330, 335. Sample on asample support (not shown) that is positioned in the apertures 322, 324,326 and 328 can be contacted with a fluid such as an ion beam to ionizeand/or atomize sample for analysis. In some embodiments, the fluid cancontact the sample on one side of the holder 300 and ionized sample canexit from an opposite side of the sample holder 300.

In certain embodiments, one or both of the plates of the sample holdersdescribed herein can include a single large aperture and a suitableamount of surface area to retain the sample support in the holder whenthe two plates are engaged to each other. Referring to FIG. 5, a plate510 is shown that comprises a single aperture 512 and a frame 514 thatis sized and arranged to engage the sample support in a suitable way toretain it within the sample holder. The exact dimensions of the frame514 and/or dimensions of the opening 512 may vary depending on theparticular sample support used with the plate 510. For example, wherethe sample support is substantially rigid, the opening 512 may be madelarger than where the sample support is flexible. Similarly, where thesample support is flexible, it may be desirable to increase the overalldimensions of the frame 514 to deter flexing or bowing of the samplesupport through the aperture 512.

In certain examples, the second plate that can couple to the plate 510may have a different number of apertures such that when the second plateis engaged to the plate 510 using the retaining devices 515 and 520, aside view may appear similar to the view shown in FIG. 2, e.g., wherethe second plate includes 13 circular apertures, the side view wouldappear substantially the same as that shown in FIG. 2. If desiredhowever, the second plate may have an aperture sized similar to theaperture 512 shown in FIG. 5. Referring now to FIG. 6, a sample holder600 is shown that includes a plate 520 coupled to the plate 510. Theplate 520 comprises an aperture 522 that is generally sized and arrangedsimilar to aperture 512 of the plate 510. The plate 520 also comprises aframe 524 that can contact some portion of the sample support (notshown) to retain the sample support in the holder 600.

In certain embodiments, the plates of the sample holders describedherein may be substantially symmetric or asymmetric. Substantiallysymmetric plates are shown, for example, in FIGS. 1 and 2. In certainexamples, a side view of a first plate 710 is shown in FIG. 7A that issubstantially rectangular and comprises apertures 712, 714 and 716 andretaining devices 730 and 735. Referring to FIG. 7B, a second plate 720comprises a generally trapezoidal shape and apertures 722, 724 and 726configured to correspond to the apertures 712, 714 and 716,respectively, when the second plate 720 is engaged to the first plate710. Referring to FIG. 7C, to engage the second plate 720 to the firstplate 710, the second plate 720 would be rotated upward until the planarsurface of the second plate 720 is substantially parallel to the planarsurface of the first plate 710. In some instances, the second plate isrotated until it contacts a sample support between the first plate 710and the second plate 720. The retaining devices 730, 735 are then movedmedially until they capture some portion of the second plate 720. Asshown in FIG. 7C, the retaining devices 730, 735 need not make fullcontact with the second plate 720 but can provide sufficient contactwith the plate 720 to hold the plate 720 in a generally uprightposition.

In some examples, the apertures in the plates can be present in morethan a single row or plane to permit loading of a plurality of samplesonto the sample support holder. For ease of illustration severalexamples are described below where the first and second plates includethe same number of apertures with substantially similar geometricshapes. It will be recognized by the person of ordinary skill in theart, given the benefit of this disclosure, that the first and secondplates may have a different number of apertures. Referring to FIG. 8, aside view of a sample holder 800 is shown comprising two rows 810 and820 of apertures in each the plate of the sample holder 800. Theretaining device has been omitted from FIG. 8 for clarity. In theillustration of FIG. 8, the sample holder 800 include two aligned rowsincluding eight apertures in each row. The number of apertures may bemore than eight of fewer than eight as desired, and the geometric shapemay also be different than the circular shape shown in FIG. 8. Duringanalysis, all samples may be analyzed in one of the rows 810, 820followed by analysis of samples in the other row, or samples within thesame column may be analyzed followed by analysis of samples in anothercolumn. The exact number of rows present in the sample holder 800 canvary and in some examples, two rows, three rows, four rows, five rows ormore may be present. Where a plurality of rows are present in the sampleholder 800, it may be desirable to reduce the overall size of theapertures to provide a desired center-to-center spacing betweendifferent apertures and increases spacing between the apertures to avoidcross-contamination of samples in different apertures.

In certain embodiments and referring to FIG. 9, another example of asample holder 900 is shown. In this illustration, the sample holder 900includes a first row of apertures 910 and a second row of apertures 920that are offset from the first row 910. It may be desirable to offsetthe rows to provide increased spacing between the samples that areloaded on the sample support in the different rows. While the number ofapertures shown in the rows 910, 920 are the same, they may be differentif desired. The geometric shapes of the apertures of the rows 910, 920may also be different if desired. During analysis, all samples may beanalyzed in one of the rows 910, 920 followed by analysis of samples inthe other row, or samples within the same column may be analyzedfollowed by analysis of samples in another column. The exact number ofrows present in the sample holder 900 can vary and in some examples, tworows, three rows, four rows, five rows or more may be present. Where aplurality of rows are present in the sample holder 900, it may bedesirable to reduce the overall size of the apertures to provide adesired center-to-center spacing between different apertures andincreases spacing between the apertures to avoid cross-contamination ofsamples in different apertures.

In certain examples, the retaining devices of the sample holdersdescribed herein can take many forms including sliding devices, hole andpin devices, e.g., a hole on one plate that can receive a pin on theother plate, a hook on one plate configured to engage a boss or hole onthe other plate, a loop on one plate that can engage a boss on the otherplate or other fasteners that are effective to retain the first plateand the second plate in an engaged position but permit rapiddisengagement of the two plates for sample support loading can be used.In some examples, the retaining devices can be those without any threadson them, e.g., the retaining devices do not use screws or other threadedfasteners to retain engagement of the first plate and the second plate.In other embodiments, the retaining device is effective to functionwithout the use of an external fasteners, e.g., screws, rivets or otherfasteners that are separate from the plates. In some embodiments, theretaining device(s) are integral to one of more of the plates, whereasin other embodiments, the retaining devices can be removed from one ofthe plates to permit cleaning and can then be placed back onto the plateafter cleaning for further use. For examples, the retaining device 115can be snapped into the plate 100 or slid onto the plate 110 from theend of the plate 110 and subsequently removed for cleaning. In someembodiments, the retaining device can be configured as one or moresliding devices as shown in a side view in FIG. 10A. The sample holder1000 comprises a first plate 1010, a second plate 1020 and a singlesliding device 1030 positioned along the upper edge of the plate 1010and configured to slide along the upper edge in a direction into and outof the figure. As shown in the open position of the sample holder 1000in FIG. 10A, one position of the sliding device 1030 is configured topermit rotation of the second plate 1020 away from the first plate 1010to permit sample support loading into the sample holder 1000. A secondposition of the sliding device 1030 (see FIG. 10B) is effective toengage some portion of the plate 1020 to retain the plate 1020 in aposition that is substantially parallel to the plate 1010. A hinge orcoupler 1035 permits rotation of the plate 1020 to the upright positionshown in FIG. 10B. Once the plate 1020 is rotated upward, the slidingdevice 1030 can be moved laterally or medially (depending on the exactconfiguration of the plate 1020) to capture some portion of the plate1020 and retain it in the upright position shown in FIG. 10B. An open orvoid space 1040 is created between the plates 1010, 1020 and may beoccupied by a sample support.

In certain embodiments, the first plate 1010 can include orthogonalprojections or bosses on the surfaces to permit the retaining device1030 to slide or move between two end points. The first end point may beselected to permit rotation of the second plate 1020 away from the firstplate 1010, and the second end point may be selected such that thesecond plate 1020 will be captured by the retaining device 1030 and heldgenerally parallel to the first plate 1010. In other examples, no bossesor projections are present, and the retaining device 1030 may be slidoff the first plate 1010 by sliding it to the end of the plate 1010 andremoving it. In other instances, the first plate 1010 can include alongitudinal track or slot that engages a groove on the retaining device1030 to guide the sliding of the retaining device 1030 back and forth inthe longitudinal direction of the first plate 1010.

In examples where the retaining devices take the form other than asliding device, the first plate 1010 may include a suitable feature thatcan releasably engage or releasably receive a corresponding feature onthe second plate 1020. For example, the sliding device 1030 may beomitted and the second plate 1020 can include a boss that is configuredto engage a hole on the first plate 1010 through a friction fit to holdthe second plate 1020 to the first plate 1010 for at least some period.In other configurations, the second plate 1020 may include anelastomeric loop that can hook to a feature on the first plate 1010 toretain the first plate 1010 to the second plate 1020. Other retainingdevices may also be used to permit engagement of the second plate to thefirst plate for at least some period.

It will be recognized by the person of ordinary skill in the art, giventhe benefit of this disclosure that the plates shown in FIGS. 1-10B aremerely illustrative of the many different plate configurations that canbe used to provide sample holders. Additional components such as gasketsor seals can be present between the plates of the sample holders toprovide a tight fit of the sample support in the holder. Where gasketsare present, they may include a substantially inert material, e.g.,PEEK, such that unwanted interfering species are not produced duringsample analysis. The gaskets may be selected to provide for increased ordecreased spacing between the plates to account for differences inthickness for different sample supports. In some embodiments, one ormore of the plates may include an alignment device or mechanismconfigured to align or position the sample support between the plates.In one embodiment, the alignment mechanism may take the form of grooveson the lateral sides of one or more of the plates. In certain examples,the grooves can be designed to rest against one or more edges of thesample support to assist in positioning the sample support in the sampleholder. In other embodiments, the alignment mechanism may be a slot onone of the plates of between one of the plates. In certain embodiments,the alignment mechanism may be a track in one or both of the plates thatcan receive some portion of the bottom edge of the sample support togenerally hold the sample support upright while the plates are engagedto each other. Other alignment mechanisms to facilitate insertion of thesample support into the sample holder will be readily selected by theperson of ordinary skill in the art, given the benefit of thisdisclosure. In some examples, the sample holders described herein caninclude posts or suitable couplings to couple the sample holder to aplatform or other structure of the system. If desired, the sample holdercan be electrically grounded to prevent unwanted build-up of anelectrical charge on the surfaces of the sample holder during analysis.In some embodiments, the exact spacing of the apertures of the platescan vary from about 0.25 inches to about 0.75 inches, though the spacingmay be smaller where rows of apertures or present or may be larger whereonly a few apertures are present.

In certain embodiments, the hinge, joint or coupler that rotatablycouples the first plate and the second plate to each other can vary. Insome embodiments, the first plate can include a sleeve that is designedto receive a groove on the second plate through a friction fit. In otherembodiments, the first and second plates can be coupled to each other byinserting a pin through hinges in each of the first and second plate,e.g., the plates may be coupled in a similar manner as a door is coupledto a door frame by aligning circular openings of the first plate and thesecond plate and placing a pin through the aligned openings. In otherembodiments, one of the plates may comprise a ball and the other maycomprise a socket to facilitate the rotatable coupling of the firstplate to the second plate. In some examples, the first and second platesare permanently rotatably coupled such that they cannot be separated bymanual force without first removing a fastener such as a pin. In otherembodiments, the second plate may be designed to be removed from thefirst plate entirely be manual force to separate the plates at the jointwhere the plates are coupled. Additional configurations for rotatablycoupling the plates will be readily selected by the person of ordinaryskill in the art, given the benefit of this disclosure.

In certain embodiments, the sample holders described herein cangenerally be used with a sample support that is effective to receive asample and retain the sample for at least some period. The samplesupport can include many different configurations, shapes, materials,etc. and may be sized and arranged such that it can be sandwiched orotherwise retained between the plates of the sample holders describedherein. In some embodiments, the sample support may take the form of amesh with an effective pore size to retain the sample on the samplesupport. The pore size and configuration may be selected depending onthe form of the sample to be loaded, e.g., liquid, solid, gas,supercritical fluid, etc. While the exact material of the sample supportmay vary, the sample support typically includes, or is made of, asubstantially inert material so no interferences are created from thesample support material leaching or otherwise desorbing from the samplesupport. In some examples, the sample support can include substantiallyinert meshes such as, for example, stainless steel meshes, inertpolymeric meshes, substantially inert membranes or membrane materials orcombinations of any of them.

In a typical sampling operation, the sample can be added to the samplesupport, e.g., either directly or by suspending the sample in a liquidor dissolving the sample in a solvent, where it is retained at least fora sufficient period to permit analysis of the sample. Where the sampleis a solid, it may be crushed, pulverized, homogenized or otherwiserendered into powder or crystalline form to be loaded onto the samplesupport. A diluent or carrier can be added to the powder to clump oragglomerate the powder to facilitate loading onto the sample support.Where diluents or carriers are used, suitable materials are selected sothey do not create species that may interfere with any analysis of thesample. Where the sample is a liquid, it may be sprayed on, dropped on,pipetted on or otherwise introduced onto the sample support. In someembodiments, the sample support can be dipped into a liquid or liquidsto load the samples onto the sample support. For example, the samplesupport can be configured with individual sections that are separated byopenings and configured to be dipped or disposed into an individualreceptacle, e.g., an individual microwell, to permit dipping of thesample support into a plurality of wells in a microwell plate. Suchsample supports would permit automated sample loading and decrease theoverall time needed to load samples onto the sample support.

In certain embodiments, the sample support can first be placed in thesample holder described herein and then sample may be loaded ontoportion of the sample support that are exposed through the apertures ofthe sample holder. The sample holder with loaded samples is then placedinto an instrument for analysis. In other embodiments, the second platemay include an integral sample support that permits loading of sampleonto the integral sample support, rotatable coupling of the second plateand the first plate, engagement of the second plate by a retainingdevice of the first plate and subsequent analysis of sample on theintegral sample support. After sampling, the second plate can beremoved, cleaned and reused or it may be discarded and replaced with anadditional second plate comprising an integral sample support. It willbe recognized by the person of ordinary skill in the art, given thebenefit of this disclosure, that the first plate may instead include anintegral sample support or both the first plate and the second platescan include integral sample supports.

In some examples, the sample support can be used with a loader which cantake the form of a frame or template that mirrors the aperture spacingand size of the plates or plates of the sample holder. The samplesupport may be placed under the template or sandwiched between thetemplate, and samples can be loaded on the apertures of the template. Ifdesired, the entire sample support plus template can be loaded into thesample holder or the sample support can be separated from the templateand then loaded into the sample holder. Where the template is loadedinto the sample holder, the template can be produced using similarmaterials as those used to produce the plates or other components of thesample holders described herein.

In certain embodiments, the plates, retaining devices and othercomponents of the sample holders described herein can be produced usingone or more suitable materials that are generally inert so as to notsubstantially interfere with, or contaminate, any sample analysis. Insome embodiments, the materials may be one or more plastic materialsincluding thermoplastics and thermosets. In some embodiments, theplastic material desirably has a melting temperature of greater than 250degrees Celsius, more particularly greater than 300 degrees Celsius. Incertain embodiments, any one or more of the plates, retaining devices,joints, etc., of the sample holders described herein can include athermoplastic comprising an acrylic polymer, a fluoroplastic polymer, apolyoxymethylene polymer, a polyacrylate polymer, a polycarbonatepolymer, a polyethylene terephthalate polymer, a polyester polymer, apolyetheretherketone polymer, a polyamide polymer, a polyimide polymer,a polyamide-imide polymer, a polyaryletherketone polymer or combinationsand copolymers thereof. If desired metallic or conductive particles canbe included in the thermoplastic to facilitate electrical coupling ofthe sample holder to an electrical ground. In some embodiments, thethermoplastic used is substantially transparent when viewed with thehuman eye to facilitate, for example, positioning of the sample supportin the sample holder. In certain embodiments, the components of thesample holders can be produced using one or more substantially inertmetal materials including, for example, Inconel® alloys, titanium andtitanium alloys, aluminum and aluminum alloys, stainless steels,refractories or other suitable materials that include metals and whichare substantially inert in the use environment of the sample holder.

In certain embodiments, some components of the sample holder can beproduced using materials other than inert materials if desired. Forexample, the hinges where the plates rotatably couple to each other maygenerally be out of the fluid stream that contacts the sample and can beproduced using materials other than non-inert materials. If desired, theplates can be produced using one inert material and the retaining devicecan be produced using a different inert material. In some embodiments,the first plate and the second plate can be produced using the samematerials or different materials. In other embodiments, differentportions of a particular plate can be produced using differentmaterials.

In some embodiments, the components of the sample holders describedherein can include a material that can withstand a cleaning operationsuch as, for example, sonication, solvent washes or other cleaners canbe used to clean and/or remove any residue from the sample holder priorto reuse. In some configurations, the materials of the sample holderscan withstand such washing steps and substantially no deteriorationoccurs after washing.

In some examples, the plates can include an indicator material that isdesigned to change color or otherwise provide a visual indication thatthe plate has been used before or has exceeded its useful lifetime. Theinclusion of visual indicators may be particularly desirable where thesample holders are designed for a single use to permitcross-contamination between samples on different sample supports. Insome embodiments, the indicator may be a temperature indicator that canchange color after exposure to high temperatures. In other embodiments,the indicator may be an electrical or magnetic indicator, e.g., liquidcrystals, that can alter the overall color or optical properties of thesample holder once it has been exposed to an electrical field, magneticfield or other electrical or magnetic stimulus.

In some examples, the sample holders described herein may be used topermit direct sample analysis of a sample on the sample support loadedinto the sample holder. An illustration of a system including a directsample analysis device is shown in FIG. 11. The system 1100 generallycomprises a direct sample analysis (DSA) device 1110 fluidically coupledto an analytical device 1120. In certain embodiments, the analyticaldevice 1120 may take many forms including mass spectrometers, opticalabsorbance or emission detectors, plasma based analytical systems orother systems. In direct sample analysis, the sample can be directlyanalyzed without undergoing pre-sample preparation or purification,e.g., without being subjected to one or more purification steps,chromatographic separation steps or the like. In a typical operation,the sample is ionized after collision with an energized ion or atom,e.g., an electronically excited ion or atom. The collisional atoms aretypically provided by an ion source such as, for example, an electronionization source, a chemical ionization source, an electrosprayionization source, an atmospheric-pressure chemical ionization source, aplasma (e.g., inductively coupled plasma), glow discharge sources, fielddesorption sources, fast atom bombardment sources, thermospray sources,desorption/ionization on silicon sources, secondary ion massspectrometry sources, spark ionization sources, thermal ionizationsources, ion attachment ionization sources, photoionization or othersuitable ion sources. Energy transfer can occur between excitedmolecules from the ion source and the sample which can cause ejection ofcharged sample species from the sample support. The ejected species maybe provided to the analytical device 1120 or system, e.g., a massanalyzer, for detection. In a typical setup, the ions which are providedto the analytical device 1120 pass through an interface (not shown)which may include one or more ion guides or lenses to select an analyteof a desired mass-to-charge ratio and/or remove any interfering orunwanted species.

In certain embodiments where the analytical device 1120 takes the formof a mass spectrometer, many different types of mass analyzers can beused with the sample support holders described herein. For example,sector field mass analyzers, time of flight mass analyzers, quadrupolemass filters, ion traps, linear quadrupole ion traps, orbitraps orcyclotrons, e.g., Fourier transform ion cyclotron resonance or othersuitable mass analyzers can be used. As selected ions exit the massanalyzer they can be provided to a detector to detect a change in chargeor a current that is produced as the ions impact or travel by a surface,for example. Illustrative detectors include, but are not limited to,electron multipliers, Faraday cups, ion-to-photon detectors,microchannel plate detectors, an inductive detector or other suitabledetectors may be used. The mass spectrometer typically will include adisplay that can provide a spectrum for review by the user. While notdescribed, the mass spectrometer typically would include numerous othercomponents including a vacuum system, one or more interfaces and manyother components commonly found in mass spectrometers in use.

When introducing elements of the aspects, embodiments and examplesdisclosed herein, the articles “a,” “an,” “the” and “said” are intendedto mean that there are one or more of the elements. The terms“comprising,” “including” and “having” are intended to be open-ended andmean that there may be additional elements other than the listedelements. It will be recognized by the person of ordinary skill in theart, given the benefit of this disclosure, that various components ofthe examples can be interchanged or substituted with various componentsin other examples.

Although certain aspects, examples and embodiments have been describedabove, it will be recognized by the person of ordinary skill in the art,given the benefit of this disclosure, that additions, substitutions,modifications, and alterations of the disclosed illustrative aspects,examples and embodiments are possible.

1-70. (canceled)
 71. A method of loading a sample for direct sample analysis, the method comprising providing a sample holder comprising a first plate comprising at least one aperture to permit a sample on a sample support to be contacted by fluid for direct sample analysis, the first plate comprising a retaining device, and a second plate rotatably coupled to the first plate and comprising a corresponding aperture to the at least one aperture of the first plate, the second plate configured to rotate to engage the first plate and retain the sample support between the first plate and the second plate, in which the retaining device of the first plate engages the second plate in a first position to retain the sample support between the first plate and the second plate and disengages the second plate in a second position to permit removal of the sample support from the sample holder.
 72. The method of claim 71, further comprising providing instructions for loading the sample on the sample support.
 73. The method of claim 71, further comprising providing instructions for inserting the sample support into the sample holder.
 74. The method of claim 71, further comprising providing a sample support.
 75. The method of claim 71, further comprising providing instructions for analyzing the sample on the sample support using direct sample analysis.
 76. A method of loading a sample for direct sample analysis, the method comprising providing a sample holder configured to retain a sample support for direct sample analysis of a sample on the sample support, the sample holder comprising a first plate attached to a second plate through at least one joint, the first plate comprising a sliding device configured to hold the second plate towards the first plate in a first position and to permit rotation of the second plate away from the first plate in the second position, in which the holding of the second plate towards the first plate retains the sample support between the first plate and the second plate.
 77. The method of claim 76, further comprising providing instructions for loading the sample on the sample support.
 78. The method of claim 76, further comprising providing instructions for inserting the sample support into the sample holder.
 79. The method of claim 76, further comprising providing a sample support.
 80. The method of claim 76, further comprising providing instructions for analyzing the sample on the sample support using direct sample analysis.
 81. A method of loading a sample for direct sample analysis, the method comprising providing a sample holder comprising a first plate comprising at least one aperture to permit a sample on a sample support to be contacted by fluid for direct sample analysis, the first plate comprising a retaining device, and a second plate comprising an integral sample support and configured to removably couple to the first plate, the second plate further configured to rotate to engage the first plate, in which the retaining device of the first plate is configured to engage the second plate to the first plate in a first position and to disengage the second plate from the first plate in a second position.
 82. The method of claim 81, further comprising providing instructions for loading the sample on the sample support.
 83. The method of claim 81, further comprising providing instructions for inserting the sample support into the sample holder.
 84. The method of claim 81, further comprising providing a sample support.
 85. The method of claim 81, further comprising providing instructions for analyzing the sample on the sample support using direct sample analysis. 